Allograft rejection and tumor immunity are generally considered to be manifestations of cell-mediated immune mechanisms of which cytotoxic T lymphocytes (CTL) are of major importance. Lymphoid cells are able to generate two kinds of CTL: allogeneic, and major histocompatibility complex (MHC) restricted, hapten specific (syngeneic). Whereas allogeneic CTL are thought to be important in allograft rejection, syngeneic CTL are thought to be of importance in autoimmunity and in surveillance against autologous neoplastic cells and against infections. Although the cellular interactions involved in the generation of syngeneic CTL remain ill-defined, it appears that the mechanism of generation of both kinds of CTL is dependent on non-T, non-B, Ia+ splenic adherent cells (SAC). This project will examine the SAC subpopulations and their soluble products needed for the generation of allogeneic versus syngeneic CTL, placing the comparisons on a quantitative basis whenever possible. In particular, experiments will be performed to examine the requirement for MHC homology between SAC and responding T cells. The Ia+ non-phagocytic SAC populations will be purified and examined for their antigen-presenting function for both kinds of CTL. The SAC subpopulation which produces the soluble mediator lymphocyte activating factor or interleukin-1 (IL-1) will be characterized. Moreover, attempts will be made to delineate the MHC restriction of the soluble factors IL-1 and interleukin-2 (IL-2) as well as the mechanisms by which IL-1 enables T cells to elaborate IL-2. Work done in the first year of support included a new observation suggesting that IL-1 and IL-2 may not be involved in the generation of primary syngeneic CTL in vitro. However, normal spleen cells cultured with large doses of IL-2 preparations, in the absence of any added antigen, generated significant CTL activity against hapten-modified syngeneic spleen cells. These killer cells seemed to be different from natural killer cells on the basis of their cell surface antigen display and on the basis of their time of appearance in culture.